Phosphodiesterase 3A1 Protects the Heart Against Angiotensin II-induced Cardiac Remodeling Through Regulation of Transforming Growth Factor-β Expression

Accumulating evidence suggests that there are direct interactions between beta-adrenergic and angiotensin II signaling pathways, and beta-blockers protect the heart against angiotensin II-induced cardiac remodeling. Phosphodiesterase 3A (PDE3A) regulates beta-adrenergic receptor/protein kinase A signaling by metabolizing cAMP. Therefore, we hypothesized that overexpressed PDE3A has cardioprotective effects against angiotensin II-induced cardiac remodeling by regulating angiotensin II signaling. In the present study, we used transgenic Mice with cardiac-specific overexpressed PDE3A1. We showed that continuous administration of angiotensin II caused cardiac hypertrophy in the wild-type mouse heart, but not in the transgenic mouse heat. Angiotensin II induced cardiac fibrosis in both wild-type and transgenic mice, but the extent of fibrosis was less in transgenic mice compared to wild-type mice. Moreover, basal expression levels of transforming growth factor-beta were lower in transgenic mouse hearts, and it remained at lower levels after angiotensin II stimulation. These findings suggest that PDE3A protects the heart from angiotensin II-induced cardiac remodeling through its modulation of the functional connection between angiotensin II and transforming growth factor-beta.